tbuckley/cabot-search huggingface dataset:
A protospacer adjacent motif‐free, multiplexed, and quantitative nucleic acid detection platform with barcode‐based Cas12a activity
Authors: Miaojin Zhou, Chunhua Zhang, Miaomiao Chen, Zhiqing Hu, Menglin Li, Zhuo Li, Lingqian Wu, Desheng Liang
Journal: MedComm (2023)

Clustered regularly interspaced short palindromic repeat (CRISPR)-based biosensors have been developed to facilitate the rapid and sensitive detection of nucleic acids. However, most approaches using CRISPR-based detection have disadvantages associated with the limitations of CRISPR RNA (crRNA), protospacer adjacent motif (PAM) or protospacer flanking sequence restriction, single channel detection, and difficulty in quantitative detection resulting in only some target sites being detected qualitatively. Here, we aimed to develop a barcode-based Cas12a-mediated DNA detection (BCDetection) strategy, which overcomes the aforementioned drawbacks and enables (1) detection with a universal PAM and crRNA without PAM or crRNA restriction, (2) simultaneous detection of multiple targets in a single reaction, and (3) quantitative detection, which can significantly distinguish copy number differences up to as low as a two-fold limit. We could efficiently and simultaneously detect three β-thalassemia mutations in a single reaction using BCDetection. Notably, samples from normal individuals, spinal muscular atrophy (SMA) carriers, and SMA patients were significantly and accurately distinguished using the quantitative detection ability of BCDetection, indicating its potential application in β-thalassemia and SMA carrier screening. Therefore, our findings demonstrate that BCDetection provides a new platform for accurate and efficient quantitative detection using CRISPR/Cas12a, highlighting its bioanalytical applications.
Tissue-specific differences in the assembly of mitochondrial Complex I are revealed by a novel ENU mutation in ECSIT
Authors: Thomas Nicol, Sara Falcone, Andrew Blease, Pratik Vikhe, Gabriele Civiletto, Saleh Salman Omairi, Carlo Viscomi, Ketan Patel, Paul K Potter
Journal: Cardiovascular Research (2023)

Mitochondrial Complex I assembly (MCIA) is a multi-step process that necessitates the involvement of a variety of assembly factors and chaperones to ensure that the final active enzyme is correctly assembled. The role of the assembly factor evolutionarily conserved signalling intermediate in the toll (ECSIT) pathway was studied across various murine tissues to determine its role in this process and how this varied between tissues of varying energetic demands. We hypothesized that many of the known functions of ECSIT were unhindered by the introduction of an ENU-induced mutation, while its role in Complex I assembly was affected on a tissue-specific basis.Here, we describe a mutation in the MCIA factor ECSIT that reveals tissue-specific requirements for ECSIT in Complex I assembly. MCIA is a multi-step process dependent on assembly factors that organize and arrange the individual subunits, allowing for their incorporation into the complete enzyme complex. We have identified an ENU-induced mutation in ECSIT (N209I) that exhibits a profound effect on Complex I component expression and assembly in heart tissue, resulting in hypertrophic cardiomyopathy in the absence of other phenotypes. The dysfunction of Complex I appears to be cardiac specific, leading to a loss of mitochondrial output as measured by Seahorse extracellular flux and various biochemical assays in heart tissue, while mitochondria from other tissues were unaffected.These data suggest that the mechanisms underlying Complex I assembly and activity may have tissue-specific elements tailored to the specific demands of cells and tissues. Our data suggest that tissues with high-energy demands, such as the heart, may utilize assembly factors in different ways to low-energy tissues in order to improve mitochondrial output. These data have implications for the diagnosis and treatment of various disorders of mitochondrial function as well as cardiac hypertrophy with no identifiable underlying genetic cause.
2-<sup>18</sup>fluoro-deoxy-D-glucose Positron Emission Tomography Is a Reliable Predictor for Viable Tumor in Postchemotherapy Seminoma: An Update of the Prospective Multicentric SEMPET Trial
Authors: Maria De Santis, Alexander Becherer, Carsten Bokemeyer, Franz Stoiber, Karin Oechsle, Franz Sellner, Alois Lang, Kurt Kletter, Bernhard M. Dohmen, Christian Dittrich, Jörg Pont
Journal: Journal of Clinical Oncology (2004)

Purpose To define the clinical value of 2- 18 fluoro-deoxy-D-glucose positron emission tomography (FDG PET) as a predictor for viable residual tumor in postchemotherapy seminoma residuals in a prospective multicentric trial. Patients and Methods FDG PET studies in patients with metastatic pure seminoma who had radiographically defined postchemotherapy residual masses were correlated with either the histology of the resected lesion or the clinical outcome documented by computer tomography (CT), tumor markers, and/or physical examination during follow-up. The size of the residual lesions on CT, either &gt; 3 cm or ≤ 3 cm, was correlated with the presence or absence of viable residual tumor. Results Fifty-six FDG PET scans of 51 patients were assessable. All 19 cases with residual lesions &gt; 3 cm and 35 (95%) of 37 with residual lesions ≤ 3 cm were correctly predicted by FDG PET. The specificity, sensitivity, positive predictive value, and negative predictive value of FDG PET were 100% (95% CI, 92% to 100%), 80% (95% CI, 44% to 95%), 100%, and 96%, respectively, versus 74% (95% CI, 58% to 85%), 70% (95% CI, 34% to 90%), 37%, and 92%, respectively, for CT discrimination of the residual tumor by size (&gt; 3 cm/≤ 3 cm). Conclusion This investigation confirms that FDG PET is the best predictor of viable residual tumor in postchemotherapy seminoma residuals and should be used as a standard tool for clinical decision making in this patient group.
Circulating Angiogenic Factors and the Risk of Preeclampsia
Authors: Richard J. Levine, Sharon E. Maynard, Cong Qian, Kee-Hak Lim, Lucinda J. England, Kai F. Yu, Enrique F. Schisterman, Ravi Thadhani, Benjamin P. Sachs, Franklin H. Epstein, Baha M. Sibai, Vikas P. Sukhatme, S. Ananth Karumanchi
Journal: New England Journal of Medicine (2004)

The cause of preeclampsia remains unclear. Limited data suggest that excess circulating soluble fms-like tyrosine kinase 1 (sFlt-1), which binds placental growth factor (PlGF) and vascular endothelial growth factor (VEGF), may have a pathogenic role.
Integrin beta-like 1 mediates fibroblast–cardiomyocyte crosstalk to promote cardiac fibrosis and hypertrophy
Authors: XiaoQiang Chen, XinTao Li, XiaoYu Wu, Yu Ding, Ya Li, GenQing Zhou, Yong Wei, SongWen Chen, XiaoFeng Lu, Juan Xu, ShaoWen Liu, Jun Li, LiDong Cai
Journal: Cardiovascular Research (2023)

Crosstalk between fibroblasts and cardiomyocytes (CMs) plays a critical role in cardiac remodelling during heart failure (HF); however, the underlying molecular mechanisms remain obscure. Recently, a secretory protein, Integrin beta-like 1 (ITGBL1) was revealed to have detrimental effects on several diseases, such as tumours, pulmonary fibrosis, and hepatic fibrosis; whereas the effect of ITGBL1 on HF is unclear. The purpose of this study was to evaluate its contribution to volume overload-induced remodelling.In this study, we identified ITGBL1 was highly expressed in varied heart diseases and validated in our TAC mice model, especially in fibroblasts. To investigate the role of ITGBL1 in in vitro cell experiments, neonatal rat fibroblasts (NRCFs) and cardiomyocytes (NRCMs) were performed for further study. We found that in comparison to NRCMs, NRCFs expressed high levels of ITGBL1. Meanwhile, ITGBL1 was upregulated in NRCFs, but not in NRCMs following angiotensin-II (AngII) or phenylephrine stimulation. Furthermore, ITGBL1 overexpression promoted NRCFs activation, whereas knockdown of ITGBL1 alleviated NRCFs activation under AngII treatment. Moreover, NRCFs-secreted ITGBL1 could induce NRCMs hypertrophy. Mechanically, ITGBL1-NME/NM23 nucleoside diphosphate kinase 1 (NME1)-TGF-β-Smad2/3 and Wnt signalling pathways were identified to mediate NRCFs activation and NRCMs hypertrophy, respectively. Finally, the knockdown of ITGBL1 in mice subjected to transverse aortic constriction (TAC) surgery recapitulated the in vitro findings, demonstrating blunted cardiac fibrosis, hypertrophy, and improved cardiac function.ITGBL1 is an important functional mediator between fibroblast-cardiomyocyte crosstalk and could be an effective target for cardiac remodelling in HF patients.
Bioresorbable Mesenchymal Stem Cell‐Loaded Electrospun Polymeric Scaffold Inhibits Neointimal Hyperplasia Following Arteriovenous Fistula Formation in a Rat Model of Chronic Kidney Disease
Authors: Allan John R. Barcena, Joy Vanessa D. Perez, Marvin R. Bernardino, Jossana A. Damasco, Andrea Cortes, Huckie C. Del Mundo, Erin Marie D. San Valentin, Carleigh Klusman, Gino Martin Canlas, Francisco M. Heralde, Rony Avritscher, Natalie Fowlkes, Richard R. Bouchard, Jizhong Cheng, Steven Y. Huang, Marites P. Melancon
Journal: Advanced Healthcare Materials (2023)

Abstract Bioresorbable perivascular scaffolds loaded with antiproliferative agents have been shown to enhance arteriovenous fistula (AVF) maturation by inhibiting neointimal hyperplasia (NIH). These scaffolds, which can mimic the three‐dimensional architecture of the vascular extracellular matrix, also have an untapped potential for the local delivery of cell therapies against NIH. Hence, an electrospun perivascular scaffold from polycaprolactone (PCL) to support mesenchymal stem cell (MSC) attachment and gradual elution at the AVF's outflow vein is fabricated. Chronic kidney disease (CKD) in Sprague‐Dawley rats is induced by performing 5/6th nephrectomy, then AVFs for scaffold application are created. The following groups of CKD rats are compared: no perivascular scaffold (i.e., control), PCL alone, and PCL+MSC scaffold. PCL and PCL+MSC significantly improve ultrasonographic (i.e., luminal diameter, wall‐to‐lumen ratio, and flow rate) and histologic (i.e., neointima‐to‐lumen ratio, neointima‐to‐media ratio) parameters compared to control, with PCL+MSC demonstrating further improvement in these parameters compared to PCL alone. Moreover, only PCL+MSC significantly reduces 18 F‐fluorodeoxyglucose uptake on positron emission tomography. These findings suggest that adding MSCs promotes greater luminal expansion and potentially reduces the inflammatory process underlying NIH. The results demonstrate the utility of mechanical support loaded with MSCs at the outflow vein immediately after AVF formation to support maturation by minimizing NIH.
Body Mass Index and Associated Medical Expenditures in the US Among Privately Insured Individuals Aged 2 to 19 Years in 2018
Authors: Ashutosh Kumar, Lyudmyla Kompaniyets, Brook Belay, Samantha L. Pierce, Scott D. Grosse, Alyson B. Goodman
Journal: JAMA Pediatrics (2023)

Importance Nearly 40% of US youth aged 2 to 19 years do not have a body mass index (BMI) in the healthy weight category. However, there are no recent estimates for BMI-associated expenditures using clinical or claims data. Objective To estimate medical expenditures among US youth across all BMI categories along with sex and age groups. Design, Setting, Participants This cross-sectional study used IQVIA’s ambulatory electronic medical records (AEMR) data set linked with IQVIA’s PharMetrics Plus Claims database from January 2018 through December 2018. Analysis was performed from March 25, 2022, through June 20, 2022. It included a convenience sample of a geographically diverse patient population from AEMR and PharMetrics Plus. The study sample included privately insured individuals with a BMI measurement in 2018 and excluded patients with pregnancy-related visits. Exposure BMI categories. Main Outcomes and Measures Total medical expenditures were estimated using generalized linear model regression with γ distribution and log-link function. For out-of-pocket (OOP) expenditures, a 2-part model was used that included logistic regression to estimate the probability of positive expenditures followed by generalized linear model. Estimates were shown with and without accounting for sex, race and ethnicity, payer type, geographic region, age interacted with sex and BMI categories, and confounding conditions. Results The sample included 205 876 individuals aged 2 to 19 years; 104 066 were male (50.5%) and the median age was 12 years. Compared with those with healthy weight, total and OOP expenditures were higher for all other BMI categories. Differences in total expenditures were highest for those with severe obesity ($909; 95% CI, $600-$1218) followed by underweight ($671; 95% CI, $286-$1055) compared with healthy weight. Differences in OOP expenditures were highest for those with severe obesity ($121; 95% CI, $86-$155) followed by underweight ($117; 95% CI, $78-$157) compared with healthy weight. Having underweight was associated with higher total expenditures at ages 2 to 5 years and 6 to 11 years by $679 (95% CI, $228-$1129) and $1166 (95% CI, $632-$1700), respectively; having severe obesity was associated with higher total expenditures at ages 2 to 5 years, 6 to 11 years, and 12 to 17 years by $1035 (95% CI, $208-$1863), $821 (95% CI, $414-$1227), and $1088 (95% CI, $594-$1582), respectively. Conclusions and Relevance The study team found medical expenditures to be higher for all BMI categories when compared with those with healthy weight. These findings may indicate potential economic value of interventions or treatments aimed at reducing BMI-associated health risks.
Insulin feedback is a targetable resistance mechanism of PI3K inhibition in glioblastoma
Authors: Evan K Noch, Laura N Palma, Isaiah Yim, Nayah Bullen, Yuqing Qiu, Hiranmayi Ravichandran, Junbum Kim, Andre Rendeiro, Melissa B Davis, Olivier Elemento, David J Pisapia, Kevin Zhai, Hongbiao Carl LeKaye, Jason A Koutcher, Patrick Y Wen, Keith L Ligon, Lewis C Cantley
Journal: Neuro-Oncology (2023)

Abstract Background Insulin feedback is a critical mechanism responsible for the poor clinical efficacy of phosphatidylinositol 3-kinase (PI3K) inhibition in cancer, and hyperglycemia is an independent factor associated with poor prognosis in glioblastoma (GBM). We investigated combination anti-hyperglycemic therapy in a mouse model of GBM and evaluated the association of glycemic control in clinical trial data from patients with GBM. Methods The effect of the anti-hyperglycemic regimens, metformin and the ketogenic diet, was evaluated in combination with PI3K inhibition in patient-derived GBM cells and in an orthotopic GBM mouse model. Insulin feedback and the immune microenvironment were retrospectively evaluated in blood and tumor tissue from a Phase 2 clinical trial of buparlisib in patients with recurrent GBM. Results We found that PI3K inhibition induces hyperglycemia and hyperinsulinemia in mice and that combining metformin with PI3K inhibition improves the treatment efficacy in an orthotopic GBM xenograft model. Through examination of clinical trial data, we found that hyperglycemia was an independent factor associated with poor progression-free survival in patients with GBM. We also found that PI3K inhibition increased insulin receptor activation and T-cell and microglia abundance in tumor tissue from these patients. Conclusion Reducing insulin feedback improves the efficacy of PI3K inhibition in GBM in mice, and hyperglycemia worsens progression-free survival in patients with GBM treated with PI3K inhibition. These findings indicate that hyperglycemia is a critical resistance mechanism associated with PI3K inhibition in GBM and that anti-hyperglycemic therapy may enhance PI3K inhibitor efficacy in GBM patients.
Low-Density Lipoprotein Cholesterol Levels in Adults With Coronary Artery Disease in the US, January 2015 to March 2020
Authors: Rahul Aggarwal, Nicholas Chiu, Peter Libby, William E. Boden, Deepak L. Bhatt
Journal: JAMA (2023)

This study uses National Health and Nutrition Examination Survey data to examine lipid control among adults in the US with coronary artery disease from January 2015 to March 2020.
Global, Regional, and National Epidemiology of Diabetes in Children From 1990 to 2019
Authors: Kexin Zhang, Chengxia Kan, Fang Han, Jingwen Zhang, Chuanhua Ding, Zhentao Guo, Na Huang, Yang Zhang, Ningning Hou, Xiaodong Sun
Journal: JAMA Pediatrics (2023)

Importance Diabetes in children is a global epidemic that causes various medical conditions associated with an increased incidence of premature death. Objective To investigate the trends in diabetes incidence, mortality, and disability-adjusted life-years (DALYs) in children, with risk factors for diabetes-associated death, from 1990 to 2019. Design, Setting, and Participants This was a cross-sectional study that used data from the Global Burden of Diseases (GBD) 2019 in 204 countries and territories. Children with diabetes who were aged 0 to 14 years were included in the analysis. Data were analyzed from December 28, 2022, to January 10, 2023. Exposure Childhood diabetes from 1990 to 2019. Main Outcome Measures Incidence, all-cause and cause-specific deaths, DALYs, and corresponding estimated annual percentage changes (EAPCs). These trends were stratified according to region, country, age, sex, and Sociodemographic Index (SDI). Results A total of 1 449 897 children (738 923 male [50.96%]) were included in the analysis. In 2019, there were 227 580 incident cases of childhood diabetes worldwide. Cases of childhood diabetes increased by 39.37% (95% uncertainty interval [UI], 30.99%-45.45%) from 1990 to 2019. Over 3 decades, diabetes-associated deaths decreased from 6719 (95% UI, 4823-8074) to 5390 (95% UI, 4450-6507). The global incidence rate increased from 9.31 (95% UI, 6.56-12.57) to 11.61 (95% UI, 7.98-15.98) per 100 000 population; however, the diabetes-associated death rate decreased from 0.38 (95% UI, 0.27-0.46) to 0.28 (95% UI, 0.23-0.33) per 100 000 population. Among the 5 SDI regions, the low SDI region had the highest childhood diabetes-associated mortality rate in 2019. Regionally, North Africa and the Middle East had the largest increase in incidence (EAPC, 2.06; 95% CI, 1.94-2.17). Among 204 countries, Finland had the highest national incidence of childhood diabetes in 2019 (31.60 per 100 000 population; 95% UI, 22.65-40.36), Bangladesh had the highest diabetes-associated mortality rate (1.16 per 100 000 population; 95% UI, 0.51-1.70), and the United Republic of Tanzania had the highest DALYs rate (100.16 per 100 000 population; 95% UI, 63.01-155.88). Globally, environmental/occupational risk, nonoptimal temperature, high temperature, and low temperature were key risk factors for childhood diabetes-associated mortality in 2019. Conclusions and Relevance Childhood diabetes is an increasing global health challenge with rising incidence. Results of this cross-sectional study suggest that despite the global decline in deaths and DALYs, the number of deaths and DALYs remains high among children with diabetes, especially in low SDI regions. Improved understanding of the epidemiology of diabetes in children may facilitate prevention and control.
Predicting progression in very thin melanoma: the challenge of the next decade?
Authors: Simone Ribero, Pietro Quaglino, Gabriele Roccuzzo
Journal: British Journal of Dermatology (2023)

Journal Article Corrected proof Predicting progression in very thin melanoma: the challenge of the next decade? Get access Simone Ribero, Simone Ribero Department of Medical Sciences, Section of Dermatology, University of Turin, Turin, Italy Correspondence: Simone Ribero. Email: simone.ribero@unito.it Search for other works by this author on: Oxford Academic Google Scholar Pietro Quaglino, Pietro Quaglino Department of Medical Sciences, Section of Dermatology, University of Turin, Turin, Italy Search for other works by this author on: Oxford Academic Google Scholar Gabriele Roccuzzo Gabriele Roccuzzo Department of Medical Sciences, Section of Dermatology, University of Turin, Turin, Italy Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, ljad218, https://doi.org/10.1093/bjd/ljad218 Published: 03 July 2023 Article history Received: 18 June 2023 Published: 03 July 2023 Corrected and typeset: 28 July 2023
Cardiovascular Disease Prevention Recommendations From an Online Chat-Based AI Model
Authors: George A. Gellert, Jakub Jaszczak
Journal: JAMA (2023)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Journals JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
Chief Residency—More Than Just Teaching and Scheduling
Authors: William K. Silverstein, Lynfa Stroud, Jonathan S. Zipursky
Journal: JAMA Internal Medicine (2023)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Internal Medicine HomeNew OnlineCurrent IssueFor Authors Podcast Journals JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Internal Medicine journal
Cancer Incidence Drop in 2020 May Not Be Real
Journal: Cancer Discovery (2023)

Abstract Cancer statistics from the Centers for Disease Control and Prevention and the NCI show a sharp drop in cancer incidence in 2020, which likely reflects pandemic-related disruptions rather than a true decline. Experts suspect that delays in screenings and diagnoses will result in more late-stage diagnoses and deaths from cancer in the coming years, particularly among certain populations with the largest declines in incidence.